The long term objective of this work is to identify the mechanism by which nitrosamines cause cancer and to find a method to disrupt that sequence. A shorter term objective is to establish the precise nature of the metabolites of nitrosamines which are responsible for the alkylation of nucleic acids. Information is being sought on the metabolism of phenylmethylnitrosamine and how the metabolites interact with genetic material. The possibility that beta and alpha hydroxylation of long-chain dialkylnitrosamines lead to direct acting carcinogens is being examined in model systems and in vivo. Preparation of alpha-oxidized dialkylnitrosamines is being attempted using both model hydroxylating systems and rational syntheses. Target molecules are alpha-amino- and alpha-hydroxy nitrosamines. A novel class of oxidized nitrosamines, the epoxynitrosamines, will be prepared and subjected to in vivo testing. Model hydroxylating systems are being studied.